Rates of women who are opting for preventive mastectomies, such as Angeline Jolie, have increased by an estimated 50 percent in recent years, experts say. But many doctors are puzzled because the operation doesn't carry a 100 percent guarantee, it's major surgery -- and women have other options, from a once-a-day pill to careful monitoring.

The results show that testosterone and estrogen have opposite effects on a gene nicknamed RORA. In neurons, testosterone lowers the ability of cells to express, or turn on, the RORA gene, while estrogen raises it.

"Autism has a huge sex bias, and it's been proposed that higher levels of fetal testosterone may put a fetus at risk," said study researcher Valerie Hu, professor of biochemistry and molecular biology at George Washington University in Washington, D.C. "We've provided an explanation of how this works."

Normally, RORA's job in cells is to turn on several other genes, Hu said. When a cell has high levels of testosterone, RORA levels run low, which affects every gene that RORA is supposed to turn on. The researchers based their findings on tests of neurons growing in lab dishes.

The research does not show that low levels of RORA cause autism, only that they are associated with the condition, Hu said. But other research has suggested that a RORA deficiency could explain many of the effects seen in autism.

This means that females may have be protected against autism — even if RORA levels were otherwise low, estrogen can "pick up some of the slack," Hu said.

"We're not saying that RORA is the only gene" involved in autism, "but it's likely one of the critical ones," Hu said.

The findings fit with ideas about autism proposed by researchers led by Simon Baron-Cohen, the director of the Autism Research Centre at the University of Cambridge in England, Hu said. Baron-Cohen proposed that high levels of testosterone in a fetus were correlated with autistic traits, and his work has demonstrated that high testosterone levels in the amniotic fluid are associated with the condition.

Rates of women who are opting for preventive mastectomies, such as Angeline Jolie, have increased by an estimated 50 percent in recent years, experts say. But many doctors are puzzled because the operation doesn't carry a 100 percent guarantee, it's major surgery -- and women have other options, from a once-a-day pill to careful monitoring.

Hu said her new study adds to that work by proposing a mechanism linking testosterone with autistic behaviors.

However, other researchers have explained autism's higher prevalence in males differently, Hu said. They suggest that genes on the X chromosome play a role in autism. Because females have two X chromosomes, and males have only one (combined with a Y chromosome), females have a "backup" copy of any gene that is mutated.

Although this theory is plausible, to date, no genes on the X chromosome have unequivocally been associated with autism, Hu said.

The new findings are published in the February issue of the journal Public Library of Science ONE.